Interleukin-17 and Interleukin-23: A Narrative Review of Mechanisms of Action in Psoriasis and Associated Comorbidities.

Psoriasis is an immune-mediated inflammatory skin disease associated with numerous inflammatory comorbidities, including increased cardiovascular risk. The interleukin (IL)-23/IL-17 axis plays a central role in the immunopathogenesis of psoriasis and related comorbidities by acting to stimulate keratinocyte hyperproliferation and feed-forwarding circuits of perpetual T cell-mediated inflammation. IL-17 plays an important role in the downstream portion of the psoriatic inflammatory cascade. This review discusses the distinct mechanisms of action of IL-17 and IL-23 in the immunopathogenesis of psoriasis and related comorbidities plus the significant therapeutic benefits of selectively inhibiting these cytokines in patients with moderate to severe plaque psoriasis.

Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.

Ixekizumab in the treatment of moderate-to-severe plaque psoriasis: Patient adherence, satisfaction, and preferences.

Ixekizumab is a humanized monoclonal antibody that exhibits its immunomodulatory effects by binding to interleukin 17A (IL-17A), a proinflammatory cytokine. It was approved for the treatment of plaque psoriasis by the Food and Drug Administration in 2016. Ixekizumab has demonstrated superiority in clinical trials against etanercept, with no significant difference in the side effect profile. The chronicity of psoriasis requires continual treatment to achieve disease clearance. Many factors may affect adherence to treatment including patient satisfaction, patient preferences, medication cost, and medication side effects. Limited data on patient adherence, satisfaction, and preference exists in formal literature. Often, surrogate measures must be used to extrapolate information regarding these measures. In this narrative review, we describe patient adherence, satisfaction, and preferences via both direct and surrogate measures as they relate to ixekizumab treatment for moderate-to-severe plaque psoriasis.

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus).

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients.

Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses important clinical questions that arise in psoriasis management and provides evidence-based recommendations. Attention will be given to pediatric patients with psoriasis, recognizing the unique physiology, pharmacokinetics, and patient-parent-provider interactions of patients younger than 18 years old. The topics reviewed here mirror those discussed in the adult guideline sections, excluding those topics that are irrelevant to, or lack sufficient information for, pediatric patients.

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world's population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments.

Clinical utility of secukinumab in moderate-to-severe scalp psoriasis: evidence to date.

Psoriasis is an immune-mediated inflammatory dermatosis commonly affecting the scalp and fringes of the face, neck and ears. It may be difficult to treat and the presence of extensive and highly visible lesions may significantly influence psychosocial well-being. Secukinumab, a monoclonal antibody that selectively targets interleukin-17A and has been shown to provide robust and sustained efficacy for whole body psoriasis. In this review, we evaluate the evidence to date of secukinumab in patients with moderate-to-severe scalp psoriasis. A comprehensive Cochrane database and PubMed searches of all available literature in English through September 2018 was performed using the search terms: "psoriasis", "scalp" and "secukinumab". Based on current evidence, we conclude that secukinumab is efficacious and well-tolerated treatment for patients with moderate-to-severe scalp psoriasis. Further studies are however warranted.

Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations on the basis of available evidence.

Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.

Psoriasis is a chronic, inflammatory multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations based on the available evidence. The treatment of psoriasis with biologic agents will be reviewed, emphasizing treatment recommendations and the role of the dermatologist in monitoring and educating patients regarding benefits as well as associated risks.

Risankizumab: an anti-IL-23 antibody for the treatment of psoriasis.

Risankizumab, a fully human IgG monoclonal antibody inhibitor of IL-23, is a therapeutic agent currently in late stage development for use in the treatment of moderate-to-severe plaque psoriasis. It is a biologic agent similar to guselkumab and tildrakizumab which targets IL-23 specifically, and has been primarily developed for use in moderate-to-severe psoriasis. USA-based pharmaceutical company Abbvie submitted it for a Biologics License Application to the US Food and Drug Administration (FDA) in April 2018. Risankizumab is the result of a collaboration between the German company Boehringer Ingelheim and Abbvie, which together are leading the future development and commercialization of risankizumab globally. The results from Phase I to Phase III clinical trials of risankizumab show it is highly effective and its FDA-approval in 2018 is likely. In this article we provide an independent expert opinion on the efficacy and safety of risankizumab in psoriasis based on a full review of the literature.

IL-17 inhibitors for psoriasis.

The role of the Th17/interleukin (IL)-23 pathway has been well elucidated in psoriasis. The IL-17 family includes 6 cytokines: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F. Two monoclonal antibodies targeting IL-17A (secukinumab, ixekizumab) and one antibody against the IL-17 receptor (brodalumab) have been approved for the treatment of moderate-to-severe plaque psoriasis. Clinical efficacy, safety, and tolerability of each agent is reviewed.

Symptomatic hypercalcemia and scarring alopecia as presenting features of sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease most frequently affecting the lungs, lymph nodes, and eyes. Skin involvement occurs in approximately 25% to 35% of cases, with the scalp uncommonly affected. Abnormal calcium metabolism is associated with sarcoidosis and other granulomatous disorders and most commonly presents as hypercalciuria (40%-60%) and, less frequently, hypercalcemia (10%-20%). Symptomatic hypercalcemia is unusual, presenting in <5% of sarcoidosis patients, and rarely results in kidney damage. We report here a case of sarcoidosis presenting with severe symptomatic hypercalcemia (>14 mg/dL, 3.5 mmol/L), scarring alopecia, and acute-on-chronic kidney failure.

Pharmacotherapeutic approaches for treating psoriasis in difficult-to-treat areas.

INTRODUCTION: Despite great therapeutic advancements in psoriasis, four notable difficult-to-treat areas including the scalp, nails, intertriginous (including genitals), and palmoplantar regions, pose a challenge to both physicians and patients. Localized disease of these specific body regions inflicts a significant burden on patients' quality of life and requires an adequate selection of treatments. AREAS COVERED: This manuscript discusses appropriate therapies and important treatment considerations for these difficult-to-treat areas based on the available clinical data from the literature. EXPERT OPINION: Clinical trials assessing therapies for the difficult-to-treat areas have been inadequate. With the first biological clinical trial for genital psoriasis pending publication, it is with hope that other biological agents will be evaluated for region-specific psoriasis. A greater understanding of the genetic and immunologic aspects of regional psoriasis, as well as identification of unique biomarkers, will further guide management decisions. For example, the recent discovery of the IL-36 receptor gene for generalized pustular psoriasis may prove valuable for other forms of psoriasis. Ultimately, identification of the most beneficial treatments for each psoriasis subtype and difficult-to-treat area will provide patients with maximal quality of life.

Secukinumab: a review of the anti-IL-17A biologic for the treatment of psoriasis.

Psoriasis is a systemic inflammatory disease associated with numerous comorbidities and a profound impact on patients' quality of life. While its complex immune pathogenesis is still not fully delineated, current evidence supports a fundamental role of the T-helper-17 (TH-17) pathway and its related interleukin-17 (IL-17) cytokine. Thus, new antipsoriatic therapies have been developed to block this key cytokine and its downstream effects. Secukinumab is a fully humanized, monoclonal anti-IL-17A antibody, and the first in its class to be approved by the US Food and Drug Administration for the treatment of moderate to severe plaque psoriasis. It has also been approved for the treatment of active psoriatic arthritis and ankylosing spondylitis. Its clinical efficacy in plaque psoriasis has been well demonstrated in numerous phase II and III clinical trials. In addition, it has shown superiority in clinical trials to current biologic agents including etanercept and ustekinumab, with a safe adverse event profile. In correlation with excellent skin improvements, secukinumab is also associated with significant improvements in health-related quality of life measures. Thus, secukinumab offers the potential for equal, or improved, therapeutic effects compared with other biologics, and is a valuable addition to our current antipsoriatic armamentarium.

Anti-IL-23 and Anti-IL-17 Biologic Agents for the Treatment of Immune-Mediated Inflammatory Conditions.

Advancements in the immunopathogenesis of psoriasis have identified interleukin (IL)-23 and IL-17 as fundamental contributors in the immune pathways of the disease. Leveraging these promising therapeutic targets has led to the emergence of a number of anti-IL-23 and -17 biologic agents with the potential to treat multiple conditions with common underlying pathology. The unprecedented clinical efficacy of these agents in the treatment of psoriasis has paved way for their evaluation in diseases such as psoriatic arthritis, Crohn's disease, rheumatoid arthritis, in addition to other immune-mediated conditions. Here we review the IL-23/IL-17 immune pathways and discuss the key clinical and safety data of the anti-IL-23 and anti-IL-17 biologic agents in psoriasis and other immune-mediated diseases.

The impact of biologic agents on health-related quality of life outcomes in patients with psoriasis.

INTRODUCTION: Psoriasis is a common, immune-mediated skin disease often associated with significant physical and psychosocial impairment. Antipsoriatic biologic agents offer patients unparalleled treatment potential in regard to greater skin clearance and overall improved quality of life. Evaluation of the therapeutic efficacy of biologic agents on the full psoriasis disease burden must account for their impact on both physical symptoms, as well as patient-reported, health-related quality of life (HRQoL) measurements. Areas covered: Results from numerous clinical trials demonstrate the significant clinical efficacy of biological agents targeting tumor necrosis factor-α (TNF-α) and the interleukin (IL)-12/23 and IL-17 immune pathways. However, relatively limited data is available evaluating their full effect on quality of life outcomes. This review will discuss the most relevant and up-to-date clinical data on HRQoL measurements related to treatment with these aforementioned biologic agents. Expert commentary: Patient-reported outcomes (i.e. Dermatology Life Quality Index) are being used with increasing frequency in clinical trials, and provide valuable information on the impact of psoriasis on numerous aspects of day-to-day living. These outcomes must also be incorporated in clinical practice, in addition to physical assessment of disease severity, treatment decisions, and therapeutic response in the psoriasis patient population.

A review article on brodalumab in the treatment of moderate-to-severe plaque psoriasis.

Psoriasis is a chronic immune-mediated skin disorder affecting approximately 2-3% of the worldwide population. Recent advances in our understanding of the immunopathogenesis of psoriasis have resulted in novel therapeutic agents. IL-17, a pro-inflammatory cytokine, plays a pivotal role in psoriasis. Therapeutic agents targeting this cytokine have shown clinical effectiveness in the treatment of moderate-to-severe plaque psoriasis. Brodalumab, a human antibody against IL-17 receptor A, has been approved by the US FDA in February 2017, by the Japanese Pharmaceuticals and Medical Devices Agency in July 2016 and by the EMA in July 2017 for the treatment of moderate-to-severe psoriasis. This article reviews the published data relating to brodalumab for the treatment of moderate-to-severe plaque psoriasis.